Overview
| Uniprot ID | Q29554 |
|---|
| Protein Name | Trifunctional enzyme subunit alpha, mitochondrial |
|---|
| Gene Name | HADHA |
|---|
| Organism | Sus scrofa |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 129 |
EAQRTFEKLEKSTKP |
| 295 |
EKVRKQTKGLYPAPL |
| 337 |
LAMTKESKALMGLYR |
| 350 |
YRGQTLCKKNKFGAP |
| 353 |
QTLCKKNKFGAPQKE |
| 359 |
NKFGAPQKEVKHLAI |
| 386 |
VSVDKHLKTILKDAS |
| 390 |
KHLKTILKDASLPAL |
| 406 |
RGQQQVFKGLNDKVR |
| 411 |
VFKGLNDKVRKKALT |
| 415 |
LNDKVRKKALTSFER |
| 519 |
ITTEKTSKDSTASAV |
| 531 |
SAVEVGLKQGKVIIV |
| 540 |
GKVIIVVKDGPGFYT |
| 569 |
LQEGVGPKKLDSLTT |
| 605 |
HVAENLGKIFGERFA |
| 634 |
FLGRKSGKGFYVYQE |
| 644 |
YVYQEGVKNRNVNSD |
| 728 |
VDLYGAQKVVDRLRK |
| 735 |
KVVDRLRKYEAIYGK |
Function
Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions. Each beta-oxidation cycle shortens the fatty acyl-CoA by two carbons, yielding one acetyl-CoA (for the citric acid cycle), one FADH(2), and one NADH (which donate electrons to the respiratory chain for ATP production). These cycles repeat until the chain is fully degraded to acetyl-CoA units. Among the enzymes involved in this pathway, the trifunctional protein--responsible for the hydration, dehydrogenation, and thiolysis steps, shows specificity for long-chain fatty acids, such as those from dietary and stored fats. Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity. These activities have been experimentally confirmed on a few substrates derived from beta-oxidation of long-chain saturated fatty acids such as palmitate (hexadecanoate) and laurate (dodecanoate). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on other substrates, including long-chain unsaturated fatty acids such as oleate (9Z-octadecenoate), linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others. Independently of subunit beta, HADHA also exhibits a cardiolipin acyltransferase activity that participates in cardiolipin remodeling; cardiolipin is a major mitochondrial membrane phospholipid. HADHA may act downstream of Tafazzin/TAZ, that remodels monolysocardiolipin (MLCL) to a cardiolipin intermediate, and then HADHA may continue to remodel this species into mature tetralinoleoyl-cardiolipin. Has also been proposed to act directly on MLCL; capable of acylating MLCL using different acyl-CoA substrates, with highest activity for oleoyl-CoA
Protein Sequence
10
MVASRAIGSL
20
RRFTASQTLR
30
CPGYICRNFT
40
RSSALLTRTH
50
INYGVKGDVA
60
VIRINSPNSK
70
VNTLGQELHS
80
EFIEVMNEVW
90
SSSQIRSAVL
100
ISSKPGCFIA
110
GADINMLSAC
120
TTSQEVTQIS
130
QEAQRTFEKL
140
EKSTKPIVAA
150
INGTCLGGGL
160
ELAISCQYRI
170
ATKDKKTVLG
180
APEVLLGILP
190
GAGGTQRLPK
200
MVGVPAAFDM
210
MLTGRGIRAD
220
KAKKMGLVDQ
230
LVEPLGPGLK
240
PPEERTIEYL
250
EEVAVTFAKG
260
LADKKISPKR
270
DKGLVEKLTS
280
YAMSIPFVRQ
290
QIYKKVEEKV
300
RKQTKGLYPA
310
PLKIIDVVKT
320
GIEQGSDAGY
330
LSESQKFGEL
340
AMTKESKALM
350
GLYRGQTLCK
360
KNKFGAPQKE
370
VKHLAILGAG
380
LMGAGIAQVS
390
VDKHLKTILK
400
DASLPALGRG
410
QQQVFKGLND
420
KVRKKALTSF
430
ERDSLFSNLT
440
GQLDYQGFEK
450
ADMVIEAVFE
460
ELSLKHKVLK
470
EVEAVIPDHC
480
VFASNTSALP
490
ISEIAAVSKR
500
PEKVIGMHYF
510
SPVDKMQLLE
520
IITTEKTSKD
530
STASAVEVGL
540
KQGKVIIVVK
550
DGPGFYTTRC
560
LAPMMSEVLR
570
ILQEGVGPKK
580
LDSLTTSFGF
590
PVGAATLMDE
600
VGMDVAKHVA
610
ENLGKIFGER
620
FAGGNLDVLK
630
QMISKGFLGR
640
KSGKGFYVYQ
650
EGVKNRNVNS
660
DTESILASLK
670
IPSRPDISSD
680
EDIQYRLVTR
690
FVNEAVLCLQ
700
EGILATPAEG
710
DIGAVFGLGF
720
PPCLGGPFRF
730
VDLYGAQKVV
740
DRLRKYEAIY
750
GKQFTPCQLL
760
IDHASSPNKK
FFQ
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0016507 |
mitochondrial fatty acid beta-oxidation multienzyme complex |
| Cellular Component |
GO:0005743 |
mitochondrial inner membrane |
| Cellular Component |
GO:0042645 |
mitochondrial nucleoid |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Molecular Function |
GO:0018812 |
3-hydroxyacyl-CoA dehydratase activity |
| Molecular Function |
GO:0004300 |
enoyl-CoA hydratase activity |
| Molecular Function |
GO:0016509 |
long-chain (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity |
| Molecular Function |
GO:0052816 |
long-chain fatty acyl-CoA hydrolase activity |
| Molecular Function |
GO:0070403 |
NAD+ binding |
| Molecular Function |
GO:0016740 |
transferase activity |
| Biological Process |
GO:0035965 |
cardiolipin acyl-chain remodeling |
| Biological Process |
GO:0006635 |
fatty acid beta-oxidation |
Reference
[1] Fan S, Zhou R, Wen H, Ye H, Ma S et al.. Global profiling of protein lactylome in porcine granulosa cells.. J Ovarian Res 18(1):177. 2025 Aug 8. PMID: 40781717.